Previous in vivo studies on panthothenate-CoA metabolism had demonstrated increases in liver total CoA which corresponded to conditions of elevated glucagon and decreased insulin (fast or alloxan-diabetes). The rate of incorporation of (14C)-pantothenate into CoA was also elevated in livers and hearts of fasted rats relative to those receiving glucose. Evidence obtained with rat liver parenchymal cells incubated in primary cultures is consistent with regulatory mechanism in which glucagon increases the rate of (14C)-pantothenate conversion to CoA through a cAMP-mediated action requiring protein synthesis; the degree of stimulation was approximately similar for both glucagon and dibutyryl cAMP plus theophylline and both activations could be reversibly inhibited by the addition of cycloheximide. Present studies attempt to determine the metabolic consequences of altered total CoA levels in the liver by using conditions where total CoA is varied independently of homonal state by regulation of dietary pantothenate for in vivo experiments and variation of extracellular pantothenate for experiments with hepatocytes in primary culture. For instance, in the presence of glucagon plus dexamethasone total CoA levels of rat liver parenchymal cells increased by 30-50 percent in the presence of pantothenate and remained constant in pantothenate-free media. These cells will be used to compare the rates of incorporation of (14C)-lactate or pyruvate into fatty acids and cholesterol, and the rates of fatty acid oxidation to ketone bodies.